AVASCULAR NECROSIS and
(Prednisone and similar) Edited from
a Dec. 2004 article
Last update 20 July 2010
is bone death due to lack of
- It represents an inability to supply adequate blood oxygen to
- AVN is extremely rare in healthy individuals.
- There are numerous causes for AVN other than prednisone usage.
- MRI is the most
sensitive means of diagnosing AVN. MRI provides
the criterion standard of noninvasive diagnostic evaluation. It is more
sensitive than CT scanning or planar scintigraphy, and is much more
sensitive than plain film radiography for detecting AVN.
- The femoral head is the most
site for development of AVN.
- The site of necrosis is usually
immediately below the weight bearing articular surface of the bone, the
anterolateral aspect of the femoral head.
- This is the site of greatest
- AVN only occurs in fatty marrow,
contains a sparse vascular supply.
- In contrast, hematopoietic bone marrow
has a rich blood supply.
persons are at decreased
- Fat cells become smaller in this
- The space
between fat cells fills with a loose reticulum and mucoid fluid, which
are resistant to AVN.
- This is termed gelatinous
marrow and, even in the
presence of increased intramedullary pressure, intersitial fluid is
able to escape into the blood vessels leaving the spaces free to absorb
- Non-traumatic AVN is commonly
bilateral and occurs in a younger population.
bilateral AVN usually occurs at different times and progresses at
different rates in each individual hip.
- AVN demonstrates no distinguishing clinical features during
- Patients do not experience pain during the ischemic episode
(initial lack of blood flow)..
- Occult (hidden) AVN can be present for more than 5 years before
the onset of symptoms.
- Patients may be asymptomatic or may develop pain gradually and
- Patients can experience a decreased range of motion (ROM),
and walk with a limp.
- Pain can be excruciating and of sudden onset, with the
patient able to note the exact time and date it began.
- Radiographic findings may appear after a delay of several
months to years following the onset of symptoms.
- Incidence of AVN is
- The causes include greater use of exogenous steroids and an
- In the U.S.
incidence is approximately 15,000 cases per year.
- The incidence is
increased because of a greater use of exogenous steroids, an increase
in trauma, and alcohol abuse.
- The relative frequencies of the
most common causes of AVN are associated with
- Alcoholism (20-40%) and
- steroid treatment (35-40%)
- Idiopathic (causes unknown)
joint destruction resulting from deterioration and leading to a major
surgical procedure occurs within 3 years following diagnosis in 50% of
- Femoral head collapse usually occurs within 2 years after
development of hip pain.
- Sickle Cell Disease
(SCD) and the
hemoglobinopathies are the major cause of AVN in African countries such
as the Democratic Republic of the Congo (formerly Zaire).
is prevalent in southern Mediterranean Europeans and people from
- Legg-Calvé-Perthes (LCP) disease is the most common
cause of AVN in children.
- The time of onset ranges from age 3-10 years, with the
highest incidence occurring from age 6-8 years.
- The greatest incidence
is in Japanese, Mongolian, Eskimo, and Central European children, with
a low incidence in blacks and American Indians.
- LCP disease affects males 4 times more
frequently than it affects females.
- Racial Background
- Predisposing conditions, such as SCD,
are concentrated in the African American population.
- Beta thalassemia
is common in Southern Europeans and Southeast Asians.
- AVN usually occurs in patients in the
third-to-fifth decades unless predisposing conditions exist that place
different age groups at risk.
that the cause of AVN most likely is related to thrombosis or
embolization of smaller arteries of the femoral head by lipid droplets,
abnormal red blood cells (as in SCD), or nitrogen bubbles from Caisson
- Other researchers think that vasculopathy with structural
damage to the
arterial or venous walls from vasculitis,
radiation necrosis, or
release of vasoactive substances (as in Gaucher disease) is the cause.
- Still other researchers think that increased intraosseous
pressure from enlargement
of intramedullary fat cells or osteocytes is a factor.
- The consensus indicates
the cause is
multifactorial and that it is better to deal with the disease as the
end result of a number of different factors with the final common
pathway resulting in bone death and collapse of the femoral head.
possible mechanisms may be present.
- Occlusion of small vessels occurs
related to fat emboli from the liver.
- Increased intraosseous (internal to bone) pressure
a steroid-related increase in the size of the intramedullary fat cells
without an equivalent compensatory loss of trabecular and cortical bone.
- Fat emboli become hydrolyzed to free fatty acids, which
toxic to vascular endothelium, causing intravascular coagulation.
- Angiogenesis is inhibited by a reduction of proteolytic
activity by the synthesis of polyclonal antithyroid hormone receptor
alpha-1 antibody (PA).
- A direct toxic effect occurs on osteogenic (bone
- Steroid use causes conversion of hematopoietic marrow
marrow, a prerequisite for the development of AVN.
- The conversion may be related to steroid-induced
caused AVN exposure
threshold is approximately 2000 mg of prednisone administered
- However, AVN has been described following lower doses.
- The risk of AVN is greater risk in patients treated for a short
duration (6 wk) with high doses (>20 mg).
- The risk of AVN in low-dose steroid therapy is controversial.
- Studies both link such therapy to the disease and also refute
the role of such treatment.
- High doses of steroids administered within a relatively short
period are more of a causative factor than cumulative dose or duration
- AVN can
occur up to 3 years
following cessation of steroid therapy.
- Steroid-induced AVN is more severe than AVN caused by other
- Underlying demineralization and accelerated osteolysis
place the weight-bearing surface of the femoral head at increased risk
- Late complications
- Continued weigh tbearing results in flattening of the
- Capillary invasion results in articular cartilage
- Such a loss predisposes patients to ostearthritis
- Individuals with systemic lupus
erythematosus (SLE) and renal allograft recipients treated with
steroids have the highest incidence of AVN.
- Autoimmune vasculitides may present similar susceptibility.
- In renal transplantation, a high association exists between AVN
and prednisone doses greater than 100 mg/d within the first month
- AVN is uncommon in transplant recipients taking less than 100
- Risk is increased of underlying bone changes associated with
chronic renal disease, such as hypophosphatemia.
- Reducing renal bone disease with better dialysis (increasing
ionized calcium in the dialysate) and medical management significantly
reduces the incidence of AVN.
- A delay in diagnosis may occur because of pain reduction
provided by concurrent administration of steroids.
- In systemic lupus erythematosus, AVN is the dominant
orthopedic problem in patients with SLE.
- Patients with SLE with vasculitis and Raynaud syndrome
are at higher risk for developing AVN.Patients usually are younger and
have more active disease with multiple organ involvement.
hip replacement is the only treatment with a positive outcome.
- Bond decompression
accomplished by drilling into the bone to allow blood to reach the area
may postpone hip replacement.
- If necrosis isn't severe, a surgical replacement of the disease
bone may be successful.
- If AVN is in the early stages, free vascularized fibular grafting
(FVFG) can be done. In the FVFG process, blood rich bone
harvested from the patient is grafted into the damaged area. If
successful, this can postpone hip replacement. This is approved
for use in the U.K., but yet experimental in the U.S.A.
extracted and edited from http://www.emedicine.com/RADIO/topic70.htm)